Macromolecular components of cardiovascular connective tissue play an important role in maintaining the integrity of cardiovascular structures, but undergo considerable change in the development of cardiovascular diseases. These studies attempt to relate the composition and nature of connective tissue macromolecules in cardiovascular diseases, especially atherosclerosis. Currently, proteoglycans present in bovine aorta are being characterized and at least two such macromolecules have been identified - a hybrid including chondroitin sulfates and dermatan sulfate in a protein core with a molecular weight of 72,000 and another proteoglycan which contains heparan sulfate covalently linked to a protein. Selective enzymatic digestion and extraction techniques have indicated a somewhat specific interaction between these proteoglycans and the fibrous structures collagen and elastin. Proteoglycan material containing heparan sulfate has been isolated and seems to have a close association with elastin in the aorta. Unlike cartilage chondromucoprotein, the aorta proteoglycans do not seem to aggregate in ultracentrifuge studies in a similar fashion. Further, they contain a large amount of hyaluronic acid. The linkage glycoproteins have not yet been identified. In other studies the interaction of lipoproteins and glycosaminoglycans are being investigated. Serum lipoproteins have been isolated from fatty streaks and fibrous plaques from human aortas with atherosclerosis. Selective enzymatic digestions with collagenase and elastase provide means of extracting essentially all of the macromolecular lipids from atherosclerotic lesions that are associated with glycosaminoglycan materials. The exact nature of the glycosaminoglycans involved in lesions interacting with lipids is not known. Hyaluronic acid is present in large quantities in the complexes of lipoproteins-glycosaminoglycans and its role has not yet been established. Studies of the basic components of cardiovascular connective tissue in the atherosclerotic lesions will aid in understanding the pathogenesis of atherosclerosis.